孕期乙醇暴露所致高脂饮食子代大鼠糖代谢功能改变

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (1): 20-26.

孕期乙醇暴露所致高脂饮食子代大鼠糖代谢功能改变

李霞^1,2，肖笛^1,2，寇皓^1,2，张郦^1,2，纪振宇^1,2，郭喻^1,2，汪晖^1,2

¹武汉大学基础医学院药理学系，武汉 430071，湖北; ² 发育源性疾病湖北省重点实验室，武汉 430071，湖北

收稿日期:2016-09-21 修回日期:2016-12-26 出版日期:2017-01-26 发布日期:2017-01-23
通讯作者: 郭喻，女，副教授，硕士生导师，研究方向：药物毒理与药物代谢研究。 Tel：13545075514 E-mail：guoy@whu.edu.cn
作者简介:李霞，女，硕士在读，研究方向：药物毒理与药物代谢研究。 Tel：15927586313 E-mail：15927586313@163.com
基金资助:
国家自然科学基金项目（81220108026；81473290）

Prenatal ethanol exposure induces dysfunction of glucose metabolism in rats fed by high-fat diet

LI Xia ^1,2, XIAO Di ^1,2, KOU Hao ^1,2, ZHANG Li ^1,2, JI Zhenyu ^1,2, GUO Yu ^1,2, WANG Hui ^1,2

¹Department of Pharmacology, School of Basic Medical Sciences, Wuhan 430071, Hubei, China;² Hubei Provincial Key Laboratory of Developmentally Originated Disease, Basic Medical College, Wuhan University, Wuhan 430071, Hubei, China

Received:2016-09-21 Revised:2016-12-26 Online:2017-01-26 Published:2017-01-23

摘要/Abstract

摘要：

目的:观察孕期乙醇暴露（prenatal ethanol exposure，PEE）对高脂饮食诱导下的成年子代糖代谢功能的影响。方法: Wistar孕鼠自受孕11 d灌胃给予乙醇（4 g·kg-1·d-1）或等容量生理盐水至分娩。仔鼠断奶后均给予高脂饮食，于出生后第20周（postnatal week 20,PW20）行糖耐量实验。PW24处死动物并检测胰腺病理形态，取肝脏检测胰岛素信号通路关键基因的mRNA表达。结果: 与对照组相比，PEE子代PW1体质量均降低（P<0.01），出生后体质量增长率显著升高（P<0.01），且胰岛病理损伤更为明显；PEE子代基础血胰岛素较对照组低，给予糖负荷后，雄、雌子代血胰岛素分泌明显增加，但绝对胰岛素水平仍低于对照组。PEE组雌性子代胰岛素敏感指数增加（P<0.05），但糖耐量异常；PEE子代肝脏胰岛素信号通路关键基因mRNA水平显著升高（P<0.05）。结论:PEE子代在高脂饮食诱导下出现追赶性生长，胰腺糖代谢功能下降但仍有代偿作用，肝脏胰岛素敏感性增加，以雌性更为明显。

关键词: 糖代谢功能, 高脂饮食, 孕期乙醇暴露

Abstract:

AIM: To investigate the effects of prenatal ethanol exposure (PEE) on glucose metabolism in rats fed by high-fat diet. METHODS: The maternal Wistar rats were administered with ethanol (4 g·kg^-1·d^-1) from gestational day-11 until full-term parturition, while the control rats were given the same volume of normal saline. All pups were fed with high-fat diet after weaning until postnatal week (PW) 20. And they were subjected to oral glucose tolerance test (OGTT) at PW 20 and sacrificed at PW 24. The morphology of the pancreas was presented by Hematoxylin-Eosin staining, and mRNA expression of key genes of hepatic insulin signaling pathwaywas was measured by real-time PCR. RESULTS: Compared with the control offspring, the body weight of the PEE offspring rats was lower (P<0.01) at PW1, and the body gain rates increased significantly after birth (P<0.01); high-fat diet induced more severe damage in pancreas of the PEE rats; the basic serum insulin level of PEE rats was lower, the release of serum insulin increased after glucose loading, but the absolute insulin level was still lower than that of the control group; the mRNA expression of key genes inhepatic insulin signaling pathway increased significantly(P<0.01). CONCLUSION: PEE rats fed with high-fat diet present obvious catch-up growth pattern and decreased pancreatic glucose metabolism, while the insulin sensitivity increases, especially in the female rats.

Key words: glucose metabolism, high-fat diet, prenatal ethanol exposure

中图分类号:

R965.2

李霞，肖笛，寇皓，张郦，纪振宇，郭喻，汪晖. 孕期乙醇暴露所致高脂饮食子代大鼠糖代谢功能改变[J]. 中国临床药理学与治疗学, 2017, 22(1): 20-26.

LI Xia, XIAO Di, KOU Hao, ZHANG Li, JI Zhenyu, GUO Yu, WANG Hui. Prenatal ethanol exposure induces dysfunction of glucose metabolism in rats fed by high-fat diet[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(1): 20-26.

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